Currently, PVL negative CA-MRSA strains belonging to some successful PVL positive CA-MRSA clones (ST1, ST59, ST5) or to the new one (ST72) have been detected, particularly in Europe and Asian-Pacific countries [1, 19–21]. In the case of the CA-MRSA IE reported here, the molecular typing revealed that although these strains share the same successful lineage ST5 with CA-MRSA (ST5-IV) and -HA-MRSA (ST5-I) epidemic clones disseminated in this country, their PFGE pattern is closer to that of the CA-MRSA clone (one band of difference with I1, additional Figure 3). Moreover, this isolate carries the SCCmec type IV and is non-multiresistant to antibiotics. Consequently, results identify a PVL-negative variant (PVL-) of the ST5-IV CA-MRSA epidemic clone detected in Argentina. Importantly, this clone belongs to lineage ST5, which has been demonstrated  to develop the VISA phenotype, but so far associated to HA-MRSA clones (ST5-II), unlike our case. These characteristics could confer another selective advantage for its dissemination in Argentina and neighboring countries.
Presently, strains of MRSA demonstrating the h-VISA or VISA phenotype have been reported in many countries worldwide, but in Latin America, cases with these phenotypes have been reported only in Northern countries and Brazil [3, 5]. Furthermore, only one case of CA-MRSA infective endocarditis from Brazil has been reported for South America, but not associated to a h-VISA strain like our case. In Argentina, the h-VISA phenotype in MRSA strains was detected for the first time in 2009. Thus, our case is the first one associated to persistent bacteremia under vancomycin therapy. Three additional cases were independently detected in Buenos Aires during the same year (presented at "Congreso Argentino de Infectología -SADI 2010" and at "XX-Congreso Latinoamericano de Microbiología; Montevideo-2010", unpublished data). Even in infections with "high-risk" of presence of h-VISA phenotype, such as IE, the prevalence of h-VISA varies significantly and is potentially associated with non-clinical factors, such as geographic location . Hence, the knowledge about general and molecular epidemiology of h-VISA phenotype in different countries is essential for effective prevention and therapy.
On the other hand, the cases of CA-MRSA IE subsequently published occurred in healthy young patients without classical risk factors for IE . This report, along with another case of CA-MRSA IE recently described in Italy,  support the importance of considering this emergent pathogen as a potential cause of IE for subjects with risk for IE (elderly patients, pre-existing heart diseases, etc). Hence, our report adds new information about CA-MRSA associated to h-VISA phenotype epidemiology, which is a matter of great interest in clinical microbiology and molecular epidemiology worldwide.
In addition, our case highlights the difficulties of laboratory detection of h-VISA-phenotype, particularly when it is unstable and arises from a fully susceptible VSSA isolate (vancomycin MIC ≤1 μg/ml) under treatment with vancomycin. Furthermore, upon detection, the choice of appropriate therapy still remains difficult [5, 6]. Daptomycin, vancomycin, teicoplanin, linezolid, TMP-SMX, and quinupristin-dalfopristin are potential options for the treatment of MRSA bacteraemia [6, 23, 24]. The treatment of our patient raises several questions and reflects the lack of evidence-based data to guide the choice of therapy for CA-MRSA IE caused for isolates expressing h-VISA phenotype with vancomycin MICs of 2 μg/ml [5, 6]. Our patient received vancomycin as first line therapy at recommended doses [6, 23]. However, due to the clinical worsening of the patient, which prevented the valvular surgery, in addition to the presence of brain abscesses, we decided to add TMP-SMX to vancomycin, even before knowing that vancomycin MIC value had risen to 2 μg/ml. TMP-SMX has bactericidal activity in-vitro and it may be considered to be an alternative therapy to vancomycin for MRSA infection [6, 24–26]. In our patient, although the last set of blood cultures may have been negative for different reasons, including changes in renal function, TMP-SMX apparently contributed to bacteraemia clearance. Only few cases of patients with persistent bacteraemia have been treated with TMP-SMX in addition to vancomycin, late in the course of bacteriemia, but these are not enough to assess the clinical outcome . Daptomycin was not considered due to the potential risks in patients with bacteremia, in which a deep focus of infection has not been surgically debrided, as well as for patients with left-side endocarditis , two characteristics seen in our patient.
One of the limitations of this report is the absence of measurements of vancomycin serum concentrations due to technical problems of the clinical laboratory at that time. Hence, although we think that, considering the clinical characteristics of the patient, the dose of vancomycin that she received should have been enough to reach or even exceed the recommended therapeutic level [6, 27], we cannot demonstrate it. In summary, the failure of vancomycin to eradicate this CA-MRSA strain was likely due to the presence of several important factors: I) high-bacterial-load during infection, combined with the impossibility to perform the cardiac surgery, II) slow bactericidal mechanism of vancomycin, III) the ability of this CA-MRSA clone to develop h-VISA phenotype and IV) the virulence of the CA-MRSA strain, possibly related to the metastatic complications and rapid progression [5, 23].